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Biallelic pathogenic variants in the TARS2 gene cause combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early‐onset severe axial hypotonia, limb hypertonia, delayed psychomotor development, epilepsy, and brain anomalies. Currently, eight COXPD21 patients have been reported in the literature, and 11 pathogenic variants in TARS2 have been identified. Here, we report a 2‐year‐6‐month‐old Chinese female who presented with severe dystonia, developmental regression, absent speech, and intractable epilepsy. Laboratory examination showed persistently increased serum lactate. Brain MRI showed that the head of the caudate and partial lenticular nucleus were bilateral symmetrical T2‐weighted imaging (T2WI) hyperintense and the corpus callosum was very thin. The clinical characteristics pointed to a ME. Trio‐based whole‐exome sequencing (WES) was employed to detect the causative variants. WES revealed novel compound heterozygous variants, c.470G>C (p.Thr157Arg) and c.2051C>T (p.Arg684Gln), in TARS2 in our patient that were inherited from the mother and father, respectively. Next, we systematically reviewed the available clinical features of COXPD21 patients and noticed that the reduced fetal movement observed in our patient may be a novel phenotype of COXPD21. These findings expand the mutation spectrum of TARS2 and provide insights into the genotype–phenotype relationship in COXPD21 as well as a foundation for its genetic counseling, diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective: To depict the cell landscape and molecular biological characteristics of human intrauterine adhesion (IUA) so as to better understand its immune microenvironment and provide new inspirations for clinical treatment., Methods: Four patients with IUA who underwent hysteroscopic treatment at Dongguan Maternal and Child Health Care Hospital from February 2022 to April 2022 were selected as the study subjects. Hysteroscopy was used to collect the tissues of IUA, which were graded based on the patient's medical history, menstrual history and status of IUA. Library construction, sequencing, single cell data comparison and gene expression matrix construction were carried out in strict accordance with the single cell RNA sequencing process. Thereafter, the UMAP dimension reduction analysis of cell population and genetic analysis were carried out based on the cell types., Results: A total of 27 511 cell transcripts were obtained from four moderately graded IUA tissue samples and assigned to six cell lineages including T cells, mononuclear phagocytes, epithelial cells, fibroblasts, endothelial cells and erythrocytes. Compared with normal uterine tissue cells, the four samples showed different cell distribution, and the proportions of mononuclear phagocytes and T cells in sample IUA0202204 were significantly increased, suggesting a strong cellular immune response., Conclusion: The cell diversity and heterogeneity of moderate IUA tissues have been described. Each cell subgroup has unique molecular characteristics, which may provide new clues for further study of the pathogenesis of IUA and heterogeneity among the patients.

Objective: To investigate the clinical significance of miRNA-146, OX-LDL and ROS in patients with primary ovarian insufficiency (POI)., Methods: 100 patients with POI were prospectively collected and 100 women with normal ovarian function were randomly selected as control group. Serum miRNA-146 expression level was detected by qRT-PCR and serum OX-LDL and ROS expression levels were detected by ELISA. Ovarian granulosa cells of mouse were transfected with miRNA-146 mimics or inhibitors, and then treated with OX-LDL. Cell viability, colony forming ability, apoptosis rate and toll like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) of pathway proteins were evaluated respectively., Results: Compared with control group, the expression level of miRNA-146 in POI group was significantly lower, the expression level of OX-LDL and ROS were significantly higher, and the ovarian volume and peak systolic blood flow velocity of ovarian artery were significantly decreased in POI group. Upregulation of miRNA-146 expression had a protective effect on OX-LDL injured ovarian granulosa cells, as evidenced by increased ovarian granulosa cell viability and colony number, reduced apoptosis, and downregulation of TLR4/NF-κB expression., Conclusion: miRNA-146 can target downstream TLR4/NF-κB signaling pathway affects oxidative stress and inflammatory response of POI induced by OX-LDL and ROS, and is expected to become a biomarker for early prediction of POI and a new target for treatment.

Monogenic disorders are varied and complex. Its overall incidence is high and the clinical phenotypes differ greatly, causing disability, mental retardation or death. It is an effective strategy to prevent the birth of newborns with monogenic disorders through prenatal screening and diagnosis. Cell-free fetal DNA based non-invasive prenatal testing for monogenic disorders has been applied in clinical practice. The range of diseases being tested is expanding, and the technology is continuously making breakthroughs. This article has provided a review over the research progress made in this field.

Metabolomics can indicate the physiological and biochemical responses of mosquitoes to different stimulants, including insecticides, which allow them to adapt to different inhospitable environments. Though metabolic differences between insecticide-resistant and -susceptible strains have been established for other mosquito species, such as Anopheles and Culex, it is yet to be done for Aedes albopictus (Skuse). In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis performed on Ae. albopictus deltamethrin-resistant and -susceptible strains showed significant differences in amino acid, organic acid, and sugar metabolism. Concentrations of neutral amino acids and sugars tended to be lower in the deltamethrin-resistant strain than in the deltamethrin-suceptible strain, but the concentration of basic and acidic amino acids and organic acids increased. All these changes might accommodate biochemical and physiological needs in deltamethrin-resistant mosquitoes, such as enzyme synthesis and detoxification. This was further confirmed by the predictable draft metabolic map. This is the first report using NMR spectroscopy to investigate the metabolic differences between deltamethrin-resistant and -susceptible strains of Ae. albopictus. To a certain degree, this demonstrates how Ae. albopictus develop insecticide resistance by metabolic reprograming to survive under the insecticide pressure., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The complete genome of the agarolytic bacterium Pseudoalteromonas sp. NJ21 from Antarctic sample was analyzed by bioinformatics methods and putative agarase aga3311was screened. Expression and characterization of the putative agarase aga3311 were studied., Methods: Gene aga3311 was cloned and expressed by genetic engineering method firstly; then, the recombinant enzyme was purified by Ni-NTA chromatography and the characterization of recombinant enzyme was determined by dinitrosalicylic acid method; the hydrolysis product of recombinant enzyme Aga3311 was analyzed by thin-layer chromatography (TLC) and mass spectrometry (MS)., Results: The recombinant expression vectors (pET-30(a)+aga3311) was overexpressed in E. coli BL21(DE3) and 30% of the recombinant protein was soluble. The purified agarase (Aga3311) revealed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with an apparent molecular weight of 87 kDa. The optimum temperature of the recombinant agarase was 35℃, and it maintained higher activity between 30 and 45℃, but the activity declined rapidly above 50℃, typical of thermal instability enzyme. The optimum pH was 7.0, and it maintained 50% of its maximum activity between pH 4 and 10. Aga3311 was significantly activated by Fe3+, Be2+, Zn2+ and Ca2+, especially Ca2+ doubled the enzyme activity. The pattern of agar hydrolysis of Aga3311 is an exo-β-agarase, producing neoagarobiose (NA2) as the final main product., Conclusion: Aga3311 is an exo-β-agarase of Glyco_hydro_42 family, producing neoagarobiose (NA2) as the final main product.